Computational chemistry is used by chemists to accelerate molecule design and optimization.
For a given target reaction, a substructural search in a reaction database (SciFinder®, Beilstein® or any other) may help a chemist to find approximately the closest reaction. Structural similarity may suggest similar conditions.
In a substructural search, the query represents a sub-graph of the target chemical reaction. Therefore, the chemist should know the database in order to create the appropriate query leading to the pertinent responses. In many cases, the search provides either too many results because the query is not selective enough or no results because the query is too selective.
A similarity search, which is in relatively wide use for individual molecules, is very rarely applied to chemical reactions because of two main problems. The first problem is related to several molecules being involved in a reaction. The second problem lies in the difficulties in taking into account distinctions between reactants and products.
The article Chemical Similarity Searching in J. Chem. Ing. Comput; Sci 1998, 38, 983-996, by P. Willett, which is hereby incorporated by reference in its entirety, reviews the use of similarity searching in chemical databases of individual molecules.
In classical similarity searching, a query may involve the specification of an entire molecule via a set of descriptors which are compared with a corresponding set of descriptors for each molecule in a database.
The procedure is based on the calculation of indices of similarity between the target molecule and each molecule of the database. Results may be represented by a ranked list in which the most similar structures to the target molecule are at the top of the list.
The article, Similarity Searching in REACCS A New Tool for the Synthetic Chemist in J. Chem. Inf. Comput. Sci. 1990, 30, 511-520, by Gretge and Moock, reviews the use of REACCS (Reaction System of the MDL company for similarity searching). REACCS determines a degree of similarity between two molecules or two reactions by calculating an amount of overlap between fragment structures.
More recently, the company ChemAxon has developed a method to calculate similarity between reactions based on fragment structures of reactants and products.
It may be desirable to provide a method for similarity searching between chemical reactions that is user friendly, efficient and easy to implement. It also may be desirable to provide a method for similarity searching between chemical reactions that may help in many areas of chemistry, like reaction searching, reagents and reaction condition selection, design of reactional pathway, exploiting laboratory notebook or piloting automated synthesis platform.